Efficacy of PI3K pathway inhibitors as single agents in metastatic breast cancer

L’objectiu del cribatge molecular és seleccionar pacients que es beneficiïn especialment de teràpies dirigides. S’analitza l’activitat en monoteràpia de fàrmacs inhibidors de la via de PI3K/AKT/mTOR (PI3Ki) en pacients amb càncer de mama metastàtic (CMM) i s’exploren potencials predictors de benefici clínic. La mitjana de temps a la progressió és de 2.6 mesos en 38 pacients incloses. No existeix correlació entre alteracions de la via i l’eficàcia, excepte en pacients amb mutació de PIK3CA que van millor al tractar-se amb un PI3Ki alfa-especific. Aquests resultats emfatitzen la necessitat d’un adequat cribatge molecular previ al tractament amb teràpies dirigides en CMM

Opportunistic screening actions for breast cancer performed by nurses working in primary health care

Abstract OBJECTIVE To identify opportunistic screening actions for breast cancer performed by nurses working in primary health care units in Ribeirão Preto, São Paulo. METHOD Cross-sectional study with 60 nurses from 28 units, who had been working for at least one year in the public municipal health care network. Data were collected between December 2013 and March 2014, by means of a questionnaire, using descriptive analysis and the software IBM SPSS version 20 and Microsoft Excel 2010. RESULTS The results showed that 71.7% of the participants questioned their female patients as for risk factors for breast cancer, mainly during nursing consultation; 70.0% oriented users about the age to perform clinical breast exam, whereas 30.0% did not due to lack of knowledge and time; 60.0% explained about the age to perform mammogram; 73.3% did not refer patients with suspicious breast exam results to the referral department, citing scheduling as the main obstacle to referral. Educational activities were not performed by 78.3% of participants. CONCLUSION Investment is needed in professional training and management of breast cancer screening.

An ultra performance liquid chromatography-tandem MS assay for tamoxifen metabolites profiling in plasma: first evidence of 4'-hydroxylated metabolites in breast cancer patients.

There is increasing evidence that the clinical efficacy of tamoxifen, the first and most widely used targeted therapy for estrogen-sensitive breast cancer, depends on the formation of the active metabolites 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen (endoxifen). Large inter-individual variability in endoxifen plasma concentrations has been observed and related both to genetic and environmental (i.e. drug-induced) factors altering CYP450s metabolizing enzymes activity. In this context, we have developed an ultra performance liquid chromatography-tandem mass spectrometry method (UPLC-MS/MS) requiring 100 μL of plasma for the quantification of tamoxifen and three of its major metabolites in breast cancer patients. Plasma is purified by a combination of protein precipitation, evaporation at room temperature under nitrogen, and reconstitution in methanol/20 mM ammonium formate 1:1 (v/v), adjusted to pH 2.9 with formic acid. Reverse-phase chromatographic separation of tamoxifen, N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen is performed within 13 min using elution with a gradient of 10 mM ammonium formate and acetonitrile, both containing 0.1% formic acid. Analytes quantification, using matrix-matched calibration samples spiked with their respective deuterated internal standards, is performed by electrospray ionization-triple quadrupole mass spectrometry using selected reaction monitoring detection in the positive mode. The method was validated according to FDA recommendations, including assessment of relative matrix effects variability, as well as tamoxifen and metabolites short-term stability in plasma and whole blood. The method is precise (inter-day CV%: 2.5-7.8%), accurate (-1.4 to +5.8%) and sensitive (lower limits of quantification comprised between 0.4 and 2.0 ng/mL). Application of this method to patients' samples has made possible the identification of two further metabolites, 4'-hydroxy-tamoxifen and 4'-hydroxy-N-desmethyl-tamoxifen, described for the first time in breast cancer patients. This UPLC-MS/MS assay is currently applied for monitoring plasma levels of tamoxifen and its metabolites in breast cancer patients within the frame of a clinical trial aiming to assess the impact of dose increase on tamoxifen and endoxifen exposure.

Abcès du sein: privilégier la ponction-aspiration échoguidée [Ultrasonography-guided drainage should be considered as the first-line approach for breast abscesses treatment].

The abscesses of the breast are puerperal or non puerperal. The Staphylococcus aureus is the most common germ. The diagnosis is based on clinical criterias and confirmed by the ultrasonography. The percutaneous ultrasonography-guided drainage must be proposed in first intent to treat. Surgical treatment is still valid with a relapsing or chronic abscess, or after the non operative processes have failed.

Breast cancer incidence in younger swiss women

Background Breast cancer in younger women has received increased attention in recent years. Although breast cancer is uncommon in young women, it is the most frequent cancer and the leading cause of cancer death for younger women in developed countries. For Switzerland, the United States and several European countries, declines in breast cancer incidence have been reported since around the year 2000, after decades of increase, among women aged 50 and older. On the other hand an increase in the incidence of breast cancer in younger women has been reported in recent years. Therefore, this study aims to evaluate time trends in breast cancer incidence in younger women in Switzerland. Methods Data on invasive breast cancer cases were obtained from the Swiss Cancer Registries of Basel, Fribourg, Geneva, Graubunden/Glarus, Jura, Neuchatel, St. Gallen-Appenzell, Ticino, Valais, Vaud and Zurich, covering the time period 1996 to 2009. Mid-year population estimates for the respective time period were supplied by the Swiss Federal Statistical Office. For females aged 20-49 years, annual age-standardized incidence rates (ASIRs) (European standard) per 100,000 person-years and corresponding 95%-confidence intervals (95% CI) were calculated. For females aged 20-39 and 40-49 years, ASIRs and incidence rate ratios (IRRs) were calculated by grouped time periods, consisting of 3-5 incidence years. IRRs and corresponding 95% CI were calculated using Poisson regression adjusting for age (reference period 1996-2000). Results ASIRs in females aged 20-49 increased gradually since 1996, being 57.36 per 100,000 person-years in 1996 (95% CI 52.54-62.51) and rising to 68.34 (95% CI 63.40-73.57) per 100,000 person-years in 2009. Comparing the time-period 2007-2009 and the reference period 1996-2000, IRRs show values of 1.17 (95% CI 1.04-1.31) for the age-group 20-39 years and 1.04 (95% CI 0.97-1.10) for the age-group 40-49 years. Conclusions Our findings confirm a slight increase in the incidence of invasive breast cancer in younger women in Switzerland during the period 1996-2009. An increase in breast cancer incidence in younger patients is an important public health problem. It warrants further investigations to identify specific risk factors of this population and to better understand the biology of this particular breast cancer.

The rise and fall in menopausal hormone therapy and breast cancer incidence.

Studies conducted in different areas of North America and Europe showed a 5-10% decline in the incidence of breast cancer following reductions up to 70% in menopause hormone therapy (HT) use after 2002. The observation that the decline was larger in (or limited to) women aged > or =50 years weighs in favour of an effect of reduced HT use on breast cancer incidence. However, changes in screening are also likely to play a role in the decreasing incidence of breast cancer observed in several countries. In particular, the technical improvements and the increased effectiveness of breast cancer screening and detection during the 1990s led to a decreased number of pre-clinical cases found by screening in subsequent years. Further, disentangling the effects of HT use and screening is difficult, as women who stop using HT may also undergo mammography screening less frequently. Thus, the reasons of the falls in incidence remain open to discussion.

Transcription factors link mouse WAP-T mammary tumors with human breast cancer.

Mouse models are important tools to decipher the molecular mechanisms of mammary carcinogenesis and to mimic the respective human disease. Despite sharing common phenotypic and genetic features, the proper translation of murine models to human breast cancer remains a challenging task. In a previous study we showed that in the SV40 transgenic WAP-T mice an active Met-pathway and epithelial-mesenchymal characteristics distinguish low- and high-grade mammary carcinoma. To assign these murine tumors to corresponding human tumors we here incorporated the analysis of expression of transcription factor (TF) coding genes and show that thereby a more accurate interspecies translation can be achieved. We describe a novel cross-species translation procedure and demonstrate that expression of unsupervised selected TFs, such as ELF5, HOXA5 and TFCP2L1, can clearly distinguish between the human molecular breast cancer subtypes-or as, for example, expression of TFAP2B between yet unclassified subgroups. By integrating different levels of information like histology, gene set enrichment, expression of differentiation markers and TFs we conclude that tumors in WAP-T mice exhibit similarities to both, human basal-like and non-basal-like subtypes. We furthermore suggest that the low- and high-grade WAP-T tumor phenotypes might arise from distinct cells of tumor origin. Our results underscore the importance of TFs as common cross-species denominators in the regulatory networks underlying mammary carcinogenesis.

Cancer du sein : la pathologie, pierre angulaire de la décision therapeutique [Breast cancer: pathology, the cornerstone of therapeutic decision]

Tailoring adjuvant therapy in breast cancer patients relies on prognostic and predictive factors, most of which are currently established by histopathological analysis of tumors. The quality of the assessment of the former (i.e.: tumor size, lymph node status, tumor grade, HER2 status, and lymphovascular invasion) and the latter (estrogen and progesteron receptors expression, HER2 overexpression or amplification) is an essential prerequisite for an optimal therapeutic decision. If the prognostic and predictive values of multigenes signatures are confirmed by on-going clinical studies, this approach could enter the clinical practice in the coming years and result in improved accuracy of adjuvant therapies in breast cancer patients. This approach might especially allow avoiding overtreatment in patients at low risk of recurrence.

Human chorionic gonadotropin in pregnancy and maternal risk of breast cancer.

Full-term pregnancies are associated with long-term reductions in maternal risk of breast cancer, but the biological determinants of the protection are unknown. Experimental observations suggest that human chorionic gonadotropin (hCG), a major hormone of pregnancy, could play a role in this association. A case-control study (242 cases and 450 controls) nested within the Northern Sweden Maternity Cohort included women who had donated a blood sample during the first trimester of a first full-term pregnancy. Total hCG was determined on Immulite 2000 analyzer. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through conditional logistic regression. Maternal breast cancer risk decreased with increasing hCG (upper tertile OR, 0.67; CI, 0.46-0.99), especially for pregnancies before age 25 (upper tertile OR, 0.41; CI, 0.21-0.80). The association diverged according to age at diagnosis: risk was reduced after age 40 (upper tertile OR, 0.60; CI, 0.39-0.91) and seemed to increase before age 40 (upper tertile OR, 1.78; CI, 0.72-4.38). Risk was reduced among those diagnosed 10 years or longer after blood draw (upper tertile OR, 0.60; CI, 0.40-0.90), but not so among those diagnosed within 10 years (upper tertile OR, 4.33; CI, 0.86-21.7). These observations suggest that the association between pregnancy hCG and subsequent maternal risk of breast cancer is modified by age at diagnosis. Although the hormone seems to be a determinant of the reduced risk around or after age 50, it might not confer protection against, or it could even increase the risk of, cancers diagnosed in the years immediately following pregnancy.

Free β-human chorionic gonadotropin, total human chorionic gonadotropin and maternal risk of breast cancer.

BACKGROUND: We investigated whether the free β-human chorionic gonadotropin (free β-hCG) would provide additional information to that provided by total hCG alone and thus be useful in future epidemiological studies relating hCG to maternal breast cancer risk. MATERIALS & METHODS: Cases (n = 159) and controls (n = 286) were a subset of our previous study within the Northern Sweden Maternity Cohort on total hCG during primiparous pregnancy and breast cancer risk. RESULTS: The associations between total hCG (hazard ratio: 0.79; 95% CI: 0.49-1.27), free β-hCG (hazard ratio: 0.85; 95% CI: 0.33-2.18) and maternal risk of breast cancer were very similar in all analyses and mutual adjustment for either one had minor effects on the risk estimates. CONCLUSION: In the absence of a reliable assay on intact hCG, total hCG alone can be used in epidemiological studies investigating hCG and breast cancer risk, as free β-hCG does not appear to provide any additional information.